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Brain Opioid Receptor Measurements by Positron Emission Tomography in Normal Cycling Women: Relationship to Luteinizing Hormone Pulsatility and Gonadal Steroid Hormones¹

Department of Gynecology and Obstetrics (Y.R.S., M.G.d.C., H.A.Z.) and Department of Radiology, Division of Nuclear Medicine (J.-K.Z., R.F.D., H.T.R., J.J.F.), The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287

Address all correspondence and requests for reprints to: J. James Frost, M.D., Ph.D., Department of Radiology, Division of Nuclear Medicine, The Johns Hopkins Medical Institutions, 600 North Wolfe Street, Nelson B1–130, Baltimore, Maryland 21287. E-mail: jfrost{at}receptor.rad.jhu.edu

The regulation of central µ-opioid receptors in women during the menstrual cycle was explored with positron emission tomography and the selective radiotracer [¹¹C]carfentanil. Ten healthy women were studied twice, during their follicular and luteal phases. Plasma concentrations of estradiol, progesterone, testosterone, and ß-endorphin were determined immediately before scanning. LH pulsatility was measured over the 9 h preceding each of the two positron emission tomography scans. No significant differences in the binding potential of µ-opioid receptors (binding capacity/K_d) were observed between phases of the menstrual cycle. However, significant negative correlations were observed between circulating levels of estradiol during the follicular phase and µ-receptor binding measures in the amygdala and hypothalamus, two regions thought to be involved in the regulation of GnRH pulsatility. LH pulse amplitude was positively correlated with µ binding in the amygdala, whereas LH pulse number was negatively correlated with binding in this same region. No significant associations were noted between LH pulse measures and the hypothalamus for this sample. These results suggest that amygdalar µ-opioid receptors exert a modulatory effect on GnRH pulsatility, and that circulating levels of estradiol also regulate central µ-opioid function.

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